LTA, LEP, and TNF-a Gene Polymorphisms are Associated with Susceptibility and Overall Survival of Diffuse Large B-Cell lymphoma in an Arab Population: A Case-Control Study

OBJECTIVE: In this study, we aimed to explore the relationship between five selected proinflammatory and immune-mediated genes (TNF rs1800629G>A, rs361525G>A, rs1799964T>C, LTA rs1800683G>A, rs909253A>G, TNFAIP8 rs1042541C>T, LEPR rs1327118G>C, and LEP rs2167270G>A) and the risk and overall survival of DLBCL patients within the Jordanian Arab population. METHODS: One hundred twenty-five patients (125) diagnosed with DLBCL at the King Abdullah University Hospital (KAUH) between 2013 and 2018 and 238 healthy cancer-free control subjects with similar geographic and ethnic backgrounds to the patients were included in the study. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissues of the subjects and from peripheral blood samples of the controls. The Sequenom MassARRAY(®) sequencer system (iPLEX GOLD) was used. The analyses included assessments of population variability and survival. RESULTS: Our study showed significant differences in the distribution of the studied polymorphisms of DLBCL between the patients and controls for TNF rs1800629G>A, LTA rs909253 G>A and LEP rs2167270 G>A. TNF rs1800629G>A (p = 0.01), in which the G allele harbors a higher risk of DLBCL (GG and GA genotypes when compared with AA genotype) (p = 0.044). The LTA rs909253 A>G polymorphism is associated with a higher risk of DLBCL in the allelic model (p = .004). LEP rs2167270 G>A polymorphism is associated with a decreased risk of DLBCL in the recessive mode models (p = .03). Subjects with the dominant model for TNF-a rs1799964 (TT genotype in comparison with the combined TT/TC genotype) and patients with the homozygous genotype (GG) of rs361525 have better overall survival rates. CONCLUSION: Our results confirmed the diversity and the heterogeneity of the disease. Although the study has a limitation because of its relatively small size, it clearly emphasizes the significance of ancestry and genetic composition as the determinants of DLBCL risk and behavior.